Near‑Infrared Driven Renal Nanomotors for Oxidative‑Stress Relief and Stone Prevention

ABSTRACT Oxidative stress is a primary pathogenic driver in the formation and progression of kidney stones. Consequently, the development of nanomaterials that mitigate oxidative stress has emerged as a promising therapeutic strategy. However, the clinical translation of most nanomedicines remains challenging due to insufficient renal targeting and accumulation. Here, we report a near‑infrared (NIR) light–driven polydopamine@polypyrrole nanomotor functionalized with hyaluronic acid (PDA@PPy@HA, PYA) for kidney‑specific targeting and enhanced on‑demand enrichment. Upon exposure to NIR light, this nanomotor converts photothermal energy into directional propulsion, thereby enhancing its accumulation within the kidneys. In vitro, PYA nanomotor alleviates high‐oxalate‐induced oxidative stress via effective elimination of reactive oxygen species (ROS) and subsequent restoration of mitochondrial membrane potential, thereby mitigating cellular apoptosis. In vivo studies further confirmed that the NIR‐driven propulsion enhanced renal accumulation of the nanomotors. This active targeting strategy resulted in the upregulation of key antioxidant enzymes, including superoxide dismutase (SOD2) and catalase (CAT), alongside the concurrent suppression of the ROS‐generating enzyme NOX2 and crystal‐adhesion molecules (OPN and CD44). Together, these molecular responses mitigate renal injury and reduce calcium oxalate deposition. Active nanomotors circumvent the limitations of passive biodistribution, enabling a potent platform for kidney stone therapy.